Background: Olaparib (ola) maintenance (mtx) improved outcomes in pts with newly diagnosed AOC and a BRCAm (DiSilvestro J Clin Oncol 2023;41:609–17) or with bev in pts with homologous recombination deficiency (HRD+) tumors (Ray-Coquard Ann Oncol 2022: LBA29) in response to 1L treatment, but an unmet need remains. Combining an immune checkpoint inhibitor with an antiangiogenic agent and a PARP inhibitor may enhance antitumor effect(Banerjee Ann Oncol 2022: 529MO).The Phase III DUO-O trial (NCT03737643) evaluates PC + bev + durva, followed by mtx bev + durva + ola, in pts with non-tBRCAm AOC in the 1L setting. Methods: Pts had newly diagnosed FIGO stage III or IV, high-grade epithelial, non-tBRCAm AOC and had completed upfront, or were planned to receive interval, debulking surgery and 1 cycle of PC ± bev. At Cycle 2, pts were randomized 1:1:1 to Arm 1: PC + bev (15 mg/kg IV q3w) + durva pbo (up to 6 cycles) followed by mtx bev (15 mg/kg IV q3w; total 15 months [mo]) + durva pbo (total 24 mo) + ola pbo (total 24 mo); Arm 2: PC + bev + durva (1120 mg IV q3w) followed by mtx bev + durva (1120 mg IV q3w) + ola pbo; or Arm 3: PC + bev + durva followed by mtx bev + durva + ola (300 mg bid tablets). The primary endpoint, progression-free survival (PFS; modified RECIST 1.1 per investigator) in Arm 3 vs Arm 1, was tested first in the non-tBRCAm HRD+ population (GIS ≥42, Myriad MyChoice CDx) and then the intent-to-treat (ITT) population. Results: 1130 pts were randomized: 378 Arm 1, 374 Arm 2, and 378 Arm 3. At a prespecified interim analysis (DCO Dec 5, 2022), a statistically significant improvement in PFS was observed for Arm 3 vs Arm 1: HR 0.49 (95% CI 0.34–0.69; P<0.0001) and HR 0.63 (95% CI 0.52–0.76; P<0.0001) in the HRD+ and ITT populations, respectively; a consistent PFS effect was observed in the HRD- subgroup (HR 0.68, 95% CI 0.54–0.86). A numerical improvement in PFS was shown for Arm 2 vs Arm 1 (ITT population), but statistical significance was not reached (Table). During the study, any serious adverse events were reported in 34%, 43% and 39% of pts in Arms 1, 2 and 3, respectively. Conclusions: PC + bev + durva followed by mtx bev + durva + ola in pts with newly diagnosed non-tBRCAm AOC resulted in a statistically significant and clinically meaningful improvement in PFS vs PC + bev followed by mtx bev. Safety was generally consistent with the known profiles of each agent. Clinical trial information: NCT03737643.

*vs Arm 1.